A Phase Ib/II Study of SYS6090 Combination Therapy in Advanced Colorectal Cancer

\*Eligibility Criteria:

Inclusion Criteria:

1. Subjects must be ≥18 years of age.
2. Histologically or cytologically confirmed unresectable advanced or metastatic colorectal cancer with pMMR/MSS status, assigned to corresponding cohorts as follows:

   Cohort 1 (2L/3L) of Phase Ib \& Phase II: Subjects must have disease progression after no more than 2 lines of standard systemic therapy (prior regimens must contain fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy); tumor tissue confirmed as pMMR by IHC or MSS by NGS/PCR; Cohort 2 (1L) of Phase Ib \& Phase II: Subjects have received no prior systemic anti-tumor therapy for advanced disease; tumor tissue confirmed as pMMR by IHC or MSS by NGS/PCR.
3. At least one extracranial measurable lesion at baseline according to RECIST 1.1 criteria.
4. Eastern Cooperative Oncology Group performance status of 0 or 1.
5. Expected survival ≥ 3 months.
6. Has protocol-defined adequate organ and bone marrow function.

Exclusion Criteria:

1. Subjects with clinically active central nervous system metastases;
2. with a history of other primary malignant tumors within 5 years before administration;
3. Subjects assigned to Cohort 1 who have received prior regorafenib treatment.;
4. Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening;
5. Uncontrolled or significant cardiovascular disease;
6. Clinically uncontrolled pleural effusion, ascites or pericardial effusion;
7. Has unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to Grade ≤ 1 or baseline .